European Journal of Pharmaceutical Sciences最新文献

{"title":"Editorial: CPH-EUFEPS 2024 Special Issue.","authors":"Judit Hohmann, Éva Szökő, Ildikó Bácskay, Tamás Tábi, Ildikó Bácskay","doi":"10.1016/j.ejps.2025.107270","DOIUrl":"10.1016/j.ejps.2025.107270","url":null,"abstract":"","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107270"},"PeriodicalIF":4.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Time shift in ciclosporin metabolism downregulation by inflammation in allogeneic hematopoietic cell transplantation: A time-dependent transduction modelling PK-PD approach","authors":"David Malnoë ,&nbsp;Tony Marchand ,&nbsp;Pascal Le Corre","doi":"10.1016/j.ejps.2025.107271","DOIUrl":"10.1016/j.ejps.2025.107271","url":null,"abstract":"<div><div>Ciclosporin is a major immunosuppressant in allogeneic hematopoietic stem cell transplantation (HSCT), with a narrow therapeutic index and high interindividual variability. We previously showed that severe inflammation significantly reduces cytochrome P450 3A4 (CYP3A4)-mediated ciclosporin metabolism, as reflected by an increased concentration-to-dose (C/D) ratio. However, the temporal dynamics between inflammation and ciclosporin metabolism remain poorly understood. This study aimed to characterize the time-dependent effect of inflammation—quantified by C-reactive protein (CRP) levels—on CYP3A4-mediated ciclosporin metabolism using a signal transduction pharmacokinetic-pharmacodynamic (PK-PD) modeling approach in HSCT patients. We selected 10 HSCT patients with a single moderate-to-severe inflammatory episode (CRP &gt; 40 mg/L) and modeled CRP kinetics alongside ciclosporin C/D ratios using a transduction model. Key parameters included the maximum effect (E_max), the CRP concentration at 50% of E_max (EC₅₀), and the time delay (τ) between CRP and metabolism variations. External validation was performed using published time profiles from Chen et al. 1994 and 2 patients with potential drug–drug interactions (pDDI) involving letermovir from our cohort. The model captured a 4.7-fold increase in C/D ratio at an EC₅₀ of 120 mg/L of CRP, with a time delay of 6 days between CRP peak and C/D ratio peak. External validation confirmed strong predictive performance. In patients with moderate-to-severe inflammation, inflammation-driven CYP3A4 downregulation appeared to outweigh the impact of letermovir-mediated DDI. Our results provide the first quantitative evidence of time-dependent inhibition due to inflammation of ciclosporin metabolism. This quantitative modeling framework may inform dose adjustment and DDI risk evaluation in inflammatory conditions, particularly in allogeneic HSCT patients.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107271"},"PeriodicalIF":4.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring polyethersulfone membranes with polycitrate for controlled transdermal delivery of azithromycin to enhance therapeutic potential","authors":"Mahya Samari ,&nbsp;Soheila Kashanian ,&nbsp;Sirus Zinadini ,&nbsp;Hossein Derakhshankhah","doi":"10.1016/j.ejps.2025.107263","DOIUrl":"10.1016/j.ejps.2025.107263","url":null,"abstract":"<div><div>This study explores the development and application of polycitrate-modified membranes for controlled drug delivery. The synthesis of polycitrate was achieved through the self-condensation of citric acid, confirmed by FT-IR spectroscopy, which indicated successful polymerization. Scanning electron microscopy revealed a two-layered membrane structure with a dense top-layer and porous sub-layers. The incorporation of polycitrate increased porosity (from 39.48 % to 64.81 %) and hydrophilicity, enhancing pore formation and drug release. Membranes with 1.5 wt. % polycitrate (M4) showed the best performance, achieving a release of 455 mg/L of azithromycin, with a zero-order release mechanism ensuring a steady rate. The optimal membrane thickness for drug release efficiency was found to be 300 µm, effectively balancing storage capacity with release characteristics. Evaluations confirmed the membranes' reusability and stability through 10 cyclic loading and sterilization processes. The increased water vapor transmission rates indicated their suitability as wound dressings, promoting an optimal healing environment. Additionally, improvements in tensile strength and controlled degradation highlight the potential of these membranes for advanced drug delivery systems. Overall, polycitrate-modified membranes emerge as a promising solution for transdermal drug delivery in clinical applications.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107263"},"PeriodicalIF":4.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated 3D printing of pediatric furosemide tablets: A personalized medicine approach using semi-solid extrusion and NIR monitoring","authors":"Farnaz Shokraneh ,&nbsp;Anne M. Filppula ,&nbsp;Aleksi Tornio ,&nbsp;Jaan Aruväli ,&nbsp;Urve Paaver ,&nbsp;Ivan Kassamakov ,&nbsp;Niklas Sandler Topelius","doi":"10.1016/j.ejps.2025.107269","DOIUrl":"10.1016/j.ejps.2025.107269","url":null,"abstract":"<div><div>This study presents the development of personalized, immediate-release furosemide tablets for pediatric use using semi-solid extrusion (SSE) 3D printing integrated with compounding system solution (CSS) technology. Dose personalization and real-time quality assurance were implemented using near-infrared (NIR) spectroscopy with partial least squares (PLS) modeling, supported by Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and surface characterization via scanning white light interferometry (SWLI).</div><div>Furosemide formulations (1 % and 2 % w/w) were prepared using a gel-based excipient and printed in doses from 2 to 10 mg. The NIR-based PLS model exhibited strong predictive accuracy (R² = 0.91; RMSEC = 3.37 %), enabling effective, non-destructive blend uniformity monitoring. All formulations met European Pharmacopoeia requirements for drug content (85.0–115.0 %) and content uniformity (AV &lt; 15). Dissolution testing confirmed rapid release profiles, with &gt;85 % release for all freshly prepared tablets. After six months, the 2 % formulation retained adequate performance (88.5 %), while the 1 % formulation showed a moderate decline (76.3 %).</div><div>FTIR and XRD analyses revealed no significant drug–excipient interactions, and the crystalline structure of furosemide remained intact throughout storage. SWLI demonstrated surface morphology variations between formulations, revealing that excipient and surfactant levels influenced microtopography and potentially drug release kinetics.</div><div>The integration of SSE 3D printing with spectroscopic and imaging tools offers a robust, reproducible, and patient-centric platform for personalized pediatric drug manufacturing. This approach supports the transition toward automated, non-sterile compounding with real-time control, improved dose precision, and enhanced product quality—addressing long-standing gaps in pediatric pharmaceutical care.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107269"},"PeriodicalIF":4.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145052404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antimicrobial core-shell nanofiber wound dressing with chloramphenicol-liposomes","authors":"Laura Victoria Schulte-Werning ,&nbsp;Ivo Laidmäe ,&nbsp;Lisa Myrseth Hemmingsen ,&nbsp;Jyrki Heinämäki ,&nbsp;Liis Preem ,&nbsp;Karin Kogermann ,&nbsp;Ann Mari Holsæter","doi":"10.1016/j.ejps.2025.107264","DOIUrl":"10.1016/j.ejps.2025.107264","url":null,"abstract":"<div><div>In the context of a rising incidence of chronic wounds worldwide, developing more efficient wound dressings is in demand. In this setting, nanofiber dressings have shown promising features. We combined three biopolymers: beta-glucan (βG), chitosan (CHI) and pectin into the same nanofibers. In addition, antimicrobial activity was provided adding chloramphenicol (CAM), which also was entrapped in liposomes for a more sustained drug release. Applying a coaxial electrospinning setup allowed fabricating core-shell nanofibers, with βG and CHI in the shell, and pectin with CAM liposomes in the core. Initially, challenges during electrospinning with gel-clogging of the needle tip emerged, due to the formation of a polyelectrolyte complex between the positively charged CHI and negatively charged pectin. This happened although pectin and CHI were separated in the coaxial electrospinning setup. Here, the critical intervention to solve this problem was reducing the pH of the pectin-containing core-solution. The successful electrospun core-shell nanofibers (Coax-LipCAM), with a mean diameter of around 200 nm, was confirmed by SEM and TEM images. Among the control nanofibers, a mono-axial control-nanofiber, Mono-core-CAM, was prepared. This control formulation contained the same polymers as present in the core of the Coax-LipCAM together with “free” CAM (not entrapped in liposomes). When Mono-core-CAM was compared with Coax-LipCAM, Coax-LipCAM exhibited enhanced tensile strength and higher stability in simulated wound fluid. Furthermore, CAM release from Coax-LipCAM was extended, with 80 % of the drug released after eight hours. Finally, all CAM-containing nanofibers showed antimicrobial activity comparable to pure CAM when tested against <em>Escherichia coli</em> and <em>S. aureus</em>. In conclusion, core-shell nanofibers with CAM-liposomes in a pectin-core and with a shell contained βG and CHI, were successfully prepared. Their promising morphological and mechanical characteristics, favorable stability and swelling properties, sustained CAM release, and preserved antimicrobial activity encourages further clinical evaluation targeting the treatment of chronic wounds.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107264"},"PeriodicalIF":4.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distinct roles of ferric carboxymaltose and ferric derisomaltose on phosphate homeostasis in iron deficiency anemia","authors":"Jessica A. Dominguez Rieg ,&nbsp;Monika Domenech Acevedo ,&nbsp;Jennifer Nogueira Coelho ,&nbsp;Monica Stevens ,&nbsp;Linto Thomas ,&nbsp;Timo Rieg","doi":"10.1016/j.ejps.2025.107265","DOIUrl":"10.1016/j.ejps.2025.107265","url":null,"abstract":"<div><div>Intravenous (IV) iron-carbohydrate nanoparticles like ferric carboxymaltose (FCM) and ferric derisomaltose (FDI) are used to treat iron deficiency anemia (IDA); however, they differ in their side-effects (e.g., hypophosphatemia). We compared the effects of FCM and FDI in a newly generated mouse model of IDA and determine their efficacy in resolving IDA and effects on mineral homeostasis. Eight-week-old female C57Bl/6J mice were fed an iron-deficient diet for 5 weeks followed by IV bleeding (0.7 % of body weight) for 3 consecutive days to establish IDA. On day 1 and 7 after induction of IDA, mice were injected with vehicle, FCM or FDI (both 20 mg kg^-1). On day 14, blood, urine and tissues were collected. Compared to baseline, all mice developed microcytic hypochromic anemia. FCM and FDI treatment resolved IDA, reversed thrombocytosis, and prevented the development splenomegaly and cardiomegaly observed in vehicle-treated anemic mice. Plasma iron increased to a greater extent with FCM versus FDI. Plasma iron showed an inverse relationship with intact fibroblast growth factor 23 (iFGF23) and C-terminal FGF23 (cFGF23). The ratio of iFGF23:cFGF23 increased in all groups but for different reasons: vehicle (iFGF23↑, cFGF23↔); FCM and FDI (iFGF23↔, cFGF23↓). The ratio was ∼1.8-fold greater in FDI versus FCM at the end of the experimental period. Only FCM caused hypophosphatemia, despite the abundance of the renal Na⁺-P_i cotransporter 2a being similarly lower (∼30 % versus vehicle) with FDI. Our results demonstrate that while FCM and FDI are equally effective at resolving IDA, hypophosphatemia is not solely caused by renal mechanisms.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107265"},"PeriodicalIF":4.7,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Simulating extractables and leachables in biopharmaceutical manufacturing to support safety assessment","authors":"Maximilian Bossong ,&nbsp;Armin Hauk ,&nbsp;Ina Pahl ,&nbsp;Roberto Menzel ,&nbsp;Peter Langguth","doi":"10.1016/j.ejps.2025.107262","DOIUrl":"10.1016/j.ejps.2025.107262","url":null,"abstract":"<div><div>The use of single-use systems in the manufacturing of biopharmaceuticals raises concerns about the accumulation of process equipment-related leachables in their production and purification processes. However, this risk is mitigated by effective sinks in the manufacturing processes and dilution of product flow, for example, in tangential-flow-filtration. This paper presents a modeling approach that combines the release and adsorption of compounds with dynamic process conditions of biopharmaceutical processes. These calculations help assess process criticality by identifying sources but also low-risk processes and components regarding extractables and leachables accumulation. This approach can significantly reduce the necessity for resource-intensive practical testing, such as leachable studies, which may be impractical from an analytical perspective due to the complex matrices in biopharmaceutical process streams.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107262"},"PeriodicalIF":4.7,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Platinum-group metal half-sandwich complexes with C-glucopyranosyl 1,2,3-triazoles and isoxazoles as ligands: synthesis and evaluation as antineoplastic and antimicrobial agents.","authors":"Rahaf Akel, Alshimaa I Zaki, Éva Kerekes, István Kacsir, György Attila Kiss, Csongor Freytag, Evelin Szoták, Dóra Boros-Pál, Eszter Anna Janka, Gábor Kardos, Péter Bai, László Somsák, Sándor Kun, Adrienn Sipos, Éva Bokor","doi":"10.1016/j.ejps.2025.107259","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107259","url":null,"abstract":"<p><p>Half-sandwich complexes of platinum-group metals are a widely studied subgroup of organometallic compounds with promising anticancer and antimicrobial properties. Recently, we have published a set of polyhapto arene/arenyl Ru(II), Os(II), Ir(III) and Rh(III) complexes with hetaryl-substituted 1-N-glucopyranosyl-1,2,3-triazole and C-glycopyranosyl-1,3,4- and -1,2,4-oxadiazole-type N,N-bidentate ligands, several of which exhibited (sub)micromolar antineoplastic and bacteriostatic potencies. The structure-activity relationships of these series indicated that the nature of the azole ring and its way of connection to the pyranoid sugar unit played crucial roles in the biological activity of such complexes. In order to further study the influence of the five-membered heteroaromatic moiety, in this work we have synthesised new complexes with O-protected 4-C-(β-D-glucopyranosyl)-1-(pyridin-2-yl)-1,2,3-triazoles and 5-C-(β-D-glucopyranosyl)-3-(pyridin-2-yl)-isoxazoles as N,N-chelating ligands of η⁶-p-cym-Ru(II)/Os(II) and η⁵-Cp*-Ir(III)/Rh(III) complexes and have studied their cytostatic and antibacterial properties. All but the Rh(III)-derived complexes exerted cytostasis on a plethora of neoplasia cell models. The Ru(II)- and Os(II)-based complexes had the best IC₅₀ values. The isoxazole-containing compounds outperformed the triazole-containing ones in terms of their cytostatic properties with submicromolar IC₅₀ values. A subset of the complexes with Ru(II) and Ir(III) ions had bacteriostatic properties with low micromolar MIC values.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107259"},"PeriodicalIF":4.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145023019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-step, chloroform-free extraction of lysophosphatidylcholine from plasma for cancer biomarker analysis","authors":"Rebecca Vieth ,&nbsp;Marilena Wittmaack ,&nbsp;Birthe Gericke ,&nbsp;Gert Fricker ,&nbsp;Ulrich Massing","doi":"10.1016/j.ejps.2025.107258","DOIUrl":"10.1016/j.ejps.2025.107258","url":null,"abstract":"<div><div>Lysophosphatidylcholine (LPC) has been the subject of research for many years, but its role in lipid turnover is still not fully understood, neither its role in cancer development and progression. A crucial aspect in LPC research is its efficient and fast extraction from plasma and tissues to use LPC as a biomarker in clinical settings. The extraction methods commonly in use like Bligh &amp; Dyer require the use of toxic halogenated solvents and are time consuming due to multiple extraction steps and subsequent solvent evaporation. In this study, a new, salt-assisted one-step extraction protocol, which avoids halogenated solvents, is presented. Saturated ammonium acetate solution was used as a salt component and acetonitrile:isopropanol (2.5:1 v/v) as eluent. The new extraction is characterized by its simplicity, robustness and short total process time of 18 minutes. For validation according to the ICH M10 guideline for bioanalytical method validation, LPC species extracted from plasma were quantified by LC-MS/MS, using LPC 19:0 as internal standard. In addition to these advantages, the new extraction procedure showed a slightly but statistically significant better recovery compared to Bligh &amp; Dyer (93.2 % vs. 87.5 %; <em>p</em> &lt; 0.05; <em>n</em> = 5), as shown by a <em>t</em>-test. The applicability of the new method was demonstrated in a pilot study, in which the plasma of 15 healthy volunteers was analyzed for its content of various LPC species.</div></div>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":"214 ","pages":"Article 107258"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing Round Window Membrane Permeability Enhancers: An Animal Study.","authors":"Jae Sang Han, Ye Lin Kim, Kyusun Park, Ji Hyung Lim, Hong-Lim Kim, So Young Park, Shi Nae Park","doi":"10.1016/j.ejps.2025.107256","DOIUrl":"https://doi.org/10.1016/j.ejps.2025.107256","url":null,"abstract":"<p><p>Intratympanic (IT) delivery of dexamethasone (DEX) is widely used for treating inner ear disorders; however, its therapeutic efficacy is limited by poor permeability of the round window membrane (RWM). This study aimed to evaluate and compare the efficacy and safety of three pharmacological agents-histamine (HIS), 3% hypertonic saline (3% HS), and sodium caprate (SC)-as adjuvants for enhancing RWM permeability and improving IT-DEX delivery in a murine model. Following IT administration of each permeability enhancer followed by DEX injection, perilymph DEX concentrations were measured using ultra-high-performance liquid chromatography, and DEX receptor expression in the organ of Corti was assessed by immunofluorescence. Structural changes in the RWM were examined by transmission electron microscopy, and auditory function was evaluated using auditory brainstem response (ABR) testing. All three enhancers significantly increased perilymph DEX concentrations compared to controls, with 3% HS demonstrating the highest levels. 3% HS also induced the greatest DEX receptor expression and caused only transient RWM structural alterations without permanent damage. Despite enhanced drug delivery, no statistically significant differences in ABR threshold recovery were observed among treatment groups. These findings demonstrate that 3% HS is the most effective adjuvant among those tested for IT drug delivery, although enhanced inner ear drug penetration does not necessarily translate to improved functional recovery in this model.</p>","PeriodicalId":12018,"journal":{"name":"European Journal of Pharmaceutical Sciences","volume":" ","pages":"107256"},"PeriodicalIF":4.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}